Ocaliva's Conditional Approval for PBC Revoked in Europe After Court Ruling

Key Insights

• The European Commission's decision to revoke the conditional marketing authorization for Ocaliva (obeticholic acid) in Europe has been upheld by the General Court of the EU.
• Advanz Pharma, which markets Ocaliva in Europe, had its temporary suspension of the revocation lifted, leading to the drug's immediate withdrawal from the EU and EEA markets.
• The revocation is based on the EMA's reassessment of Ocaliva's benefit-risk profile, concluding it was no more effective than a placebo for primary biliary cholangitis (PBC).

Advanz Pharma's Ocaliva (obeticholic acid), a treatment for primary biliary cholangitis (PBC), will no longer be available in Europe after the General Court of the European Union upheld the European Commission's decision to revoke its conditional marketing authorization (CMA). The revocation, effective immediately, impacts all European Union member states and European Economic Area countries, including Iceland, Liechtenstein, and Norway.

The decision follows a reassessment by the European Medicines Agency (EMA) of Ocaliva's benefit-risk profile. While Ocaliva had previously demonstrated a reduction in alkaline phosphatase (ALP) and bilirubin levels in PBC patients, the EMA's Committee for Medicinal Products for Human Use (CHMP) concluded that data from a confirmatory trial (NCT02308111), alongside real-world data, indicated the drug was no more effective than a placebo.

Advanz Pharma had temporarily secured a suspension of the EC’s decision while pursuing legal action. However, the General Court declined to extend the suspension, leading to the immediate withdrawal of Ocaliva from the European market. A final ruling on Advanz Pharma's challenge is expected in 2025.

Ocaliva received conditional marketing authorization in 2016, allowing its prescription for PBC patients while additional data was collected. It is indicated for use in combination with ursodeoxycholic acid (UDCA) in patients with an inadequate response to UDCA, or as a monotherapy for those unable to tolerate UDCA. PBC is a rare, progressive autoimmune condition that damages the bile ducts in the liver.

Ocaliva functions as a selective and potent farnesoid X receptor (FXR) agonist, regulating bile acid and metabolic pathways. Advanz Pharma acquired the rights to Ocaliva in Europe after acquiring non-American subsidiaries of Intercept Pharmaceuticals in July 2022 for an upfront payment of $405 million. Intercept retains the US rights to Ocaliva, where it remains available under accelerated approval. The company is in discussions with the FDA regarding the future of Ocaliva in the US market.

The FDA granted accelerated approval to Ocaliva in 2016, but added a black box warning in 2018 after reports of severe liver injury linked to incorrect dosing. Earlier this month, the FDA denied full approval for Ocaliva following a recommendation from its advisory committee, which concluded that the benefits did not outweigh the risks.